Background: The primary objective of the present investigation is to evaluate the antidiabetic, antihyperlidemic and antioxidant activity of the methanolic extract of the Paederia foetida Linn. ( PF ) leaf extract in the streptozotocin induced diabetic rats. Methods: Single intraperitoneal injection (IP) of streptozotocin (60 mg/kg body weight) was used for induction of diabetes is swiss albino (wistar strain) rats. The induction of diabetes was confirmed after 3 days as noticing the increase in blood sugar level of tested rats. PF at a once a daily dose of 100 mg/kg, 250 mg/kg, 500 mg/kg, p.o. along with glibenclamide 10 mg/kg, p.o. was also given for 28 days. On the 28 ^th day rats from all the groups fasted overnight fasted and the blood was collected from the puncturing the retro orbit of the eye under mild anesthetic condition. There collected blood sample was used to determine the antihyperlipidemic, hypoglycemic and antioxidant parameters. Results: The oral acute toxicity studies did not show any toxic effect till the dose at 2000 mg/kg. While oral glucose tolerance test showed better glucose tolerance in tested rats. The statistical data indicated that the different dose of the PF significantly increased the body weight, hexokinase, plasma insulin, high density lipoprotein cholesterol, superoxide dismutase, catalase and glutathione peroxides. It also decreases the level of fasting blood glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, malonaldehyde, glucose-6-phosphate, fructose-1-6-biphosphate and glycated hemoglobin in STZ induced diabetic rats. The histopathology of STZ induce diabetic rats, as expected the test dose of PF extract considerably modulates the pathological condition of various vital organ viz. heart, kidney, liver, pancreas as shown in the histopathology examinations. Conclusions: Our investigation has clearly indicated that the leaf extract of Paederia foetida Linn. showed remarkable antihyperglycemic activity due to its possible systematic effect involving in the pancreatic and extra pancreatic mechanism. Forever, the antihyperlipidemic activity was exerted possible by lowering the higher level of lipid profile and decreasing the intercalated disc space in the heart. The antioxidant activity of extract was due to inhibition of lipid peroxidation and increasing the SOD, GPx and CAT. It was corroborate that the extract shown the Paederia foetida Linn leaves potential to be act as antidiabetic, antihyperlipidemic and antioxidant properties.

Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response.

Cisplatin (CIS) is one of the most effective anticancer drug used in the treatment of several solid tumors .Its use is limited by its nephrotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of CIS and the possible protective effect against CIS-induced nephrotoxicity in rats. The percent survival of female tumor bearing mice was used for determination the cytotoxic activity of CIS in the presence or the absence of RSVL. Uptake and cell cycle effect, serum creatinine (CREA), blood urea nitrogen (BUN), Reduced Glutathione (GSH) and histopatholgical examination of kidney tissues after CIS and/or RSVL therapy were also investigated. RSVL increased the intracellular level of CIS in EAC cells and there was a strong correlation between the high cellular level of CIS and its cytotoxicity. CIS at a dose level of 5 mg/kg increased the mean survival time of female tumor bearing mice to 25 days compared with 17 days for tumor-bearing control mice. Administration of RSVL at a dose level of 25 mg/kg simultaneously with CIS increased the mean survival time to 48 days with 60% survival of the tumor-bearing animals. Cell cycle analysis of tumor cells showed that CIS treatment decreases the proliferation index of tumor cells while in presence of RSVL there was more significant inhibitions. Also, CIS treatment caused increase in level of creatinine and blood urea with significant decrease in the GSH level. While, in the presence of RSVL, level of creatinine and blood urea restored to control level. This study suggests that RSVL could increase the cytotoxic activity of CIS and protect against its nephrotoxicity.

Doxorubicin (DOX) is one of the most important anticancer agents used in treating breast cancer. However, chronic cardiotoxicity and multidrug resistance limit the chemotherapeutic use of DOX. This study aimed to evaluate the capability of calcium channel blocker diltiazem (DIL) to reverse DOX resistance in breast cancer MCF-7 cells and to confer protection against DOX-induced cardiotoxicity in Wistar rats. For this purpose, we explored the effects of DOX on cell cycle phase distribution and expression of ABCB1, FOXO3a, and p53 genes in the presence and absence of DIL (20 μg/ml) and studied the ability of DIL to prevent DOX-induced cardiotoxicity after a single injection of DOX (15 mg/kg) in male Wister rats. We found that compared with DOX alone treatment, DIL + DOX treatment down regulated the ABCB1 gene expression by > fourfold but up regulated the FOXO3a and p53 genes expression by 1.5 fold. DIL treatment conferred protection against DOX-induced cardiotoxicity, as indicated by a decrease in the levels of the cardiac enzyme creatine kinase MB and malondialdehyde and an increase in the total antioxidant capacity and glutathione peroxidase levels. These biochemical results were further confirmed by the histopathological investigation of cardiac cells, which showed normal cardiac cells with central vesicular nuclei and prevention of DOX-induced disruption of normal cardiac architecture in the DIL to DOX group. Taken together, our results indicate that DIL treatment can reverse the resistance of breast cancer cells to the therapeutic effects of DOX and can protect against DOX-induced cardiotoxicity in rats.

Type 2 diabetes mellitus (T2DM) is a chronic disease that affects millions of people worldwide. Metformin is the optimal initial therapy for patients with T2DM. Genetic factors play a vital role in metformin response, including variations in drug efficacy and potential side effects. To determine the effects of genetic variants of multidrug and toxin extrusion protein 2 (MATE2), ataxia telangiectasia mutated (ATM), and serine/threonine kinase 11 (STK11) genes on metformin response in a cohort of Saudi patients. This prospective observational study included 76 T2DM newly diagnosed Saudi patients treated with metformin monotherapy and 80 control individuals. Demographic data, lipid profiles, creatinine levels, and hemoglobin A1c (HbA1c) levels were collected before and after treatment. All participants were genotyped for 5 single-nucleotide polymorphisms (SNPs), including rs4621031, rs34399035, rs2301759, rs1800058, and rs11212617, using TaqMan R genotyping assays. This study included 156 subjects. The subjects’ mean ± SD age was 50.4 ± 10.14 years. The difference in HbA1c levels in T2DM after treatment ranged from −1.20% to 8.8%, with a mean value of 0.927 ± 1.73%. In general, 73.7% of the patients with T2DM showed an adequate response to metformin (HbA1c < 7%). STK11 (rs2301759) significantly affects the response to metformin in T2DM patients. In the rs2301759 single-nucleotide polymorphisms, the prevalence of an adequate response to metformin was significantly higher among patients with C/C and T/C genotypes than among non-responders (P = .021). However, no statistically significant associations were observed for the other tested SNPs. Our study provides evidence of an association between STK11 (rs2301759) and response to metformin in Saudi patients with T2DM. The need for targeted studies on specific gene-drug associations is emphasized, and further studies with a larger population should be conducted.

Backgrounds: Inter-individual variability in response to statin was mainly due to genetic differences. This study aimed to investigate the association of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) single nucleotide polymorphism (SNP) with response to simvastatin in hypercholesterolemia patients conducted at King Abdulaziz University hospital (KAUH) in Jeddah, Saudi Arabia. Patients and methods: A total of 274 participants were registered in the current study. Hypercholesterolemic patients taking simvastatin 20 mg (n = 148) and control subjects (n = 126) were tested for rs35599367 and rs776746 genotypes using Custom Taqman ® Assay Probes. Response to simvastatin in these patients was assessed by determination of low density lipoprotein (LDL-C), total cholesterol (TC) and by measuring statin plasma levels using Liquid Chromatography-Mass Spectrometry (LC-MS). Results: None of the participants carried a homozygous CYP3A4*22 mutant genotype, while 12 (4.4%) individuals had a heterozygous genotype and 262 (95.6%) had a wild homozygous genotype. The CYP3A5*3 allele was detected in the homozygous mutant form in 16 (5.8%) individuals, while 74 (27.0%) individuals carried the heterozygous genotype and 184 (67.2%) carried the wildtype homozygous genotype. Of the patient group, 15 (11%) were classified as intermediate metabolizers (IMs) and 133 (89%) as extensive metabolizers (EMs). Plasma simvastatin concentrations for the combined CYP3A4/5 genotypes were significantly (P<0.05) higher in the IMs group than in the EMs group. TC and plasma LDL-C levels were also significantly (P<0.05) higher in IMs than in EMs. Conclusion: The present study showed associations between CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) SNP combination genotypes with response to statins in hypercholesterolemia. Patients who had either a mutant homozygous allele for CYP3A5*3 or mutant homozygous and heterozygous alleles for CYP3A4*22 showed increased response to lower TC and LDL-C levels.